announcement

Read about Simons Searchlight’s commitment to data privacy and security.

Publications

Date Revised: March 2026

Thank you to all the families for participating in Simons Searchlight. Through your involvement, we aim to assist researchers and geneticists worldwide in understanding genetic disorders affecting you or your family.

The research conducted using Simons Searchlight data has resulted in numerous published papers. These papers undergo a peer-review process, where other scientists assess and validate the research before publication in scientific journals. Additionally, some findings are shared via preprints, allowing rapid dissemination of information to the scientific community.

Many of the publications feature the name “Simons Variation in Individuals Project” (SimonsVIP), which was the original name of our research program, now known as Simons Searchlight.

The listed articles are organized from newest to oldest. You can explore publications by specific genetic conditions using the categories below.

As of March 2026, Simons Searchlight has contributed to 139 publications and preprints, and we will continue to summarize new publications.

For accessibility, the Simons Foundation encourages researchers to make their publications open access. If you cannot access a journal article, we recommend reaching out to the last author listed on the paper to request a copy.

Understanding Publication Reference Titles:

-The article title is followed by publication details, including where and when it was published.
– If there are more than three authors, we use “et al.” to represent additional contributors.
– Journals are referenced using shorthand names.

Disclaimer: Please be aware that papers posted on medRxiv (pronounced med-archive) or bioRxiv (pronounced bio-archive) are not peer-reviewed or edited before online publication. In contrast, all other articles listed here have undergone review by fellow researchers to ensure quality and accuracy. While posting on medRxiv or bioRxiv allows researchers to share findings quickly, the final published results may differ after undergoing formal peer review for journal publication.

Show More
Show Less

Search

  • Filter
  • Clear All
Genetic Condition
Year of Publication
139 Publications
Parental experiences of receiving a rare genetic disease diagnosis for their child on diagnosis day
  • The researchers aimed to study the experiences of parents when receiving a rare genetic diagnosis for their child. The researchers wanted to better understand parents’ experiences to provide best practices for diagnosis delivery for healthcare providers. Show More
  • The researchers used Simons Searchlight to recruit for this study.
  • The recruited families with a child 18 years or younger who received their genetic diagnosis in the last 5 years.
  • 717 participants were included in this study, representing 229 rare diseases. About one-half of participants received their diagnosis in person and the rest received their diagnosis either by phone or telehealth.
  • Most often, a geneticist provided the diagnosis (41 percent), followed by genetic counselors (25 percent). 226 of the diagnoses were given by non-genetics providers. The researchers found an association between results being returned by non-genetics providers and the likelihood of parents responding that they would have liked something changed about their genetic results return.
  • Caregivers reported that the most important information during results return was quality of life, medical management, inheritance, and connecting with other families.
  • One-half of caregivers were provided support information at the time of diagnosis.
  • The most common emotions reported by caregivers at the time of their child’s genetic diagnosis were hopelessness, anxiety, sadness, confusion, and relief.
  • For genetic results return, about one-half of parents felt that there were areas that could have been improved. In general, areas for improvement included: (1) providing specific information on the diagnosis, (2) asking parents about their preferred method for disclosing results, (3) ensuring that all family members or support people can be present if desired, and (4) fostering an environment of compassion and empathy during the disclosure. Show Less
Am J Med Genet A 200, 67-76 (2026)
Bullock et al.
Full Article

All Genes
2026

Challenging behavior domains in individuals with neurodevelopmental genetic syndromes: The role of psychological features
  • The researchers studied problem behaviors, such as property destruction, aggression, elopement, conduct problems, and self-injury, in participants with neurodevelopmental genetic syndromes. Show More
  • The researchers recruited participants aged 3 to 45 with GRIN2B, CSNK2A1, HIVEP2, SCN2A, MED13L, ADNP, and STXBP1. The participants were recruited through Simons Searchlight and other patient advocacy foundations and non-profits.
  • The participants took five surveys that assessed problem behaviors, emotion regulation, anxiety, sensory sensitivity, and social communication.
  • The researchers found that emotion dysregulation was a strong predictor of aggression, conduct problems, and property destruction.
  • Lower levels of social communication was the strongest predictor of elopement and self-injury.
  • Different types of anxiety, such as worry or physiological, had their own associations with problem behaviors. Higher physiological anxiety, a racing heart, and being sweaty, flush, or shacky were strongly associated with elopement and aggression. Having lower worry was associated with elopement.
  • Lower levels of speech abilities was a predictor for conduct problems and elopement.
  • The researchers suggested that supporting a person through problem behaviors may require multi-faceted interventions for the child and the family, as there are links between the different behaviors. The individual’s needs, preferences, and risk of harm that may result from behaviors should be considered. Show Less
Am J Med Genet B Neuropsychiatr Genet 201, 52-63 (2026)
Ferguson et al.
Full Article

ADNP
CSNK2A1
GRIN2B
HIVEP2
MED13L
SCN2A
STXBP1
2026

A Prospective Natural History Study Protocol for Clinical Trial Readiness in Synaptic Disorders
  • The researchers created a protocol for prospective natural history data collection for STXBP1- and SYNGAP1-related disorders. A prospective natural history study is important for future therapies because it collects information from participants as they develop over time, and not only historical information. Show More
  • As genetic therapies have become more available to patient communities, understanding the natural history of rare genetic disorders has become a priority for many researchers.
  • The researchers combined in-person assessments with data from Simons Searchlight and the RARE-X registry.
  • This research is ongoing. The researchers will include 200 participants over time and complete assessments every 6 months at various clinical centers across the U.S.
  • The natural history study began in 2023, and 164 STXBP1 participants and 159 SYNGAP1 participants have been recruited thus far.
  • The majority (73 percent, 78 out of 107 people) with STXBP1-related disorder has had a seizure at any point in their lifetime. Age of onset ranged from day 0 of life to 11.7 years old, with an average age of onset of 2.5 months.
  • The majority (84 percent, 84 out of 100 people) with SYNGAP1-related disorder has had seizures at any point in their lifetime, with an average age of onset of 2.2 years.
  • The researchers suggested that parent-reported outcome measures, such as the data collected within Simons Searchlight, can offer insights into the participants that cannot be measured in a clinical setting. But, there were challenges to getting parents to complete the parent-reported surveys, even after discussion about the importance of completion with families.
  • The researchers aim to also identify biomarkers for these communities that can be used in clinical trials in the future. Show Less
medRxiv Preprint, (2026)
McKee et al.
Full Article

STXBP1
SYNGAP1
2026

Cell-type specific global reprogramming of the transcriptome and epigenome in induced neurons with the 16p11.2 neuropsychiatric CNVs
  • Mental health conditions, such as schizophrenia or anxiety, can be inherited, and researchers have been working to understand what factors may be inherited from family members. Show More
  • Since 16p11.2 deletions and 16p11.2 duplications have been linked to mental health conditions, the researchers used nine 16p11.2 deletion and five 16p11.2 duplication induced pluripotent stem cells (iPSCs) derived from Simons Searchlight participants. iPSCs are a special type of cells that can be turned into other body cells, making it easier to study parts of the body that are difficult to get samples of, such as brain cells.
  • These iPSCs were turned into different brain cells to learn which genes were turned on or off (also known as gene expression) that might lead to mental health conditions. The researchers also studied the presence of DNA methylation, a process where chemical tags are added to DNA to “silence” or turn off a genetic region.
  • Brain cells and neurons with a 16p11.2 deletion had genes within the 16p11.2 region that were less active. Whereas, brain cells and neurons with a 16p11.2 duplication had genes within the 16p11.2 region that were more active.
  • Importantly, genes outside the 16p11.2 region were also affected by changes in gene expression and DNA methylation, usually in the same direction (levels either went up in both deletions or duplications, or went down).
  • The PCSK9 gene did not follow this pattern. Gene expression in iPSCs was higher in 16p11.2 deletions and lower in 16p11.2 duplications. But, in neurons, gene expression was higher in both 16p11.2 deletions and 16p11.2 duplications. The researchers suggested that the PCSK9 gene could affect head size, brain development, and body size in people with a 16p11.2 variant.
  • To study this, the researchers used a fish model to study the PCSK9 gene, and they found that turning off the PCSK9 gene resulted in changes in embryonic and early brain development.
  • The researchers also found that in iPSCs and neurons, in both 16p11.2 deletions and 16p11.2 duplications, there was often more DNA methylation compared with cells without these variants, across many locations of DNA.
  • This work used advanced iPSC technology to help us better understand the bigger picture of what DNA in brain cells looks like in people with 16p11.2 deletions and 16p11.2 duplications. Show Less
Eur J Hum Genet Epub ahead of print, (2025)
Ward et al.
Full Article

16p11.2 deletion
16p11.2 duplication
2025

MED13L-related disorder characterized by severe motor speech impairment
  • The researchers studied the speech, language, motor, cognitive, adaptive, and behavioral features of Simons Searchlight participants with MED13L-related syndrome. They also included in-person research data collected in 2022 at a MED13L Family and Research Conference. Show More
  • Language and speech are different - language is the meaning, structure, and the way in which a person uses words, whereas speech is the physical movement and coordination of the lips, tongue, and breathing to produce sound.
  • This study included 17 people from the in-person conference and 67 online participants with likely pathogenic and pathogenic MED13L variants.
  • All in-person participants had a motor speech disorder, such as childhood apraxia of speech, dysarthria, or both. Childhood apraxia of speech is a speech disorder caused by a problem with communication between the brain and the muscles used for speaking. Dysarthria is a speech disorder that results when the muscles used to speak become paralyzed or weakened. Everyone had severe impairment in receptive language (ability to understand language) and expressive language (ability to express yourself).
  • All in-person participants had intellectual disability, and when they were able to be measured, non-verbal IQ scores were higher than verbal IQ scores. They also had deficits in visual motor integration.
  • Most Simons Searchlight participants with MED13L-related syndrome reported having a language disorder (65 out of 67 people or 97 percent). One out of 3 children were minimally verbal or non-verbal after the age of 4.
  • In-person assessment of gross and fine motor deficits were comparable to what was reported through online data collection.
  • Motor speech disorders were common in the study participants, and this was considered to be consistent with a muscular/mechanical defect rather than a purely cognitive defect.
  • The researchers collected the medical history shared with Simons Searchlight. Commonly reported issues included low muscle tone in 50 out of 60 people (83 percent); gastrointestinal problems, including constipation, gastroesophageal reflux, and diarrhea in 34 out of 60 people (57 percent); and vision problems in 43 out of 60 people (72 percent). About 1 in 3 people reported seizures (20 out of 65 people or 31 percent), and 63 out of 65 people (97 percent) reported some degree of cognitive impairment and a language disorder diagnosis. Some participants had autism spectrum disorder (28 out of 57 people or 49 percent) and attention-deficit/hyperactivity disorder (13 out of 60 people or 22 percent).
  • The researchers suggested that there might be a higher rate of germline mosaicism in the MED13L community. Germline mosaic is when a person’s egg cells or sperm cells carry the same genetic variant, but that person does not have that variant detected in blood.
  • The researchers also suggested that children with MED13L-related disorder might benefit from a referral to speech therapy to assess their needs. Show Less
J Neurodev Disord 17, 56 (2025)
Mitchel et al.
Full Article

MED13L
2025

Genetic modifiers and ascertainment drive variable expressivity of complex disorders
  • The researchers studied why people with the same genetic neurodevelopmental condition have a spectrum of medical features, and what genetic factors might result in someone having more medical issues than others. Show More
  • The researchers included data from Simons Searchlight 16p11.2 deletion and duplication participants, as well as other genetic registries with 16p12.1 deletion carriers. The researches compared the medical features between people with 16p11.2 deletions and 16p12.1 deletions.
  • In this study, almost all people with a 16p12.1 deletion inherited the variant from a parent (84 out of 90 people or 93 percent). But, most parents, siblings, and other carrier relatives had milder cognitive or psychiatric issues than the child who was first identified with the genetic diagnosis. The first person in a family diagnosed with a genetic condition is called the proband.
  • The researchers studied the medical features across 6 domains: intellectual disability/developmental delay and behavioral, psychiatric, nervous system, congenital, and growth/skeletal defects.
  • Probands had more medical features than their relatives carrying the same genetic variant, but these relatives had more features than people with no identified genetic variant in this study.
  • About one-third of probands (31 out of 99 or 31 percent) had additional, clinically relevant genetic variants. The researchers also found that clinical severity increased in people with additional variants. This suggests that additional secondary variants contribute to a person having more medical features than the carrier parent.
  • In this analysis, the researchers suggested that contributing factors to a person’s medical features included: 1) their primary diagnosed genetic condition, 2) additional genetic variants and their function, 3) medical features that are being studied and/or how the person with the genetic condition was identified, meaning if a person was identified through a particular study focused on autism, or developmental delays.
  • The researchers did not find any single secondary variant that accounted for all medical features in a person, which indicates that secondary variants modify the effects of the 16p12.1 deletion. The researchers suggested that treatments that consider the primary or first diagnosed genetic condition, as well as the second or other variants, might be beneficial for medical management. Show Less
Cell 188, 7065-7082.e17 (2025)
Jensen et al.
Full Article

16p11.2 deletion
16p11.2 duplication
2025

Comparison of autism domains across thirty rare variant genotypes
  • The researchers investigated how likely it is to develop autism across individuals with: idiopathic autism (autism with no known genetic cause), monogenic conditions (a genetic variant affecting only one neurodevelopmental gene), copy number variant conditions (larger deletions or duplications that include several genes, also called CNV), and control participants (people with no developmental or genetic diagnosis). Show More
  • The researchers collected Social Communication Questionnaire (SCQ) data from multiple cohort studies to examine the differences and similarities across groups. The SCQ is used as a tool to assess autism features in large research cohorts. A score of 22 or higher identifies that a person should have a clinical evaluation of autism, meaning that the survey is not able to provide someone with an autism diagnosis.
  • Lifetime SCQ data from 364 participants in Simons Searchlight, 309 people across 15 monogenic conditions, and 55 people across 5 CNV conditions were combined with SCQ data from other research studies.
  • The likelihood of autism was higher across monogenic conditions, with people having greater impairment than those with CNV conditions. ADNP and DYRK1A with the highest prevalence of autism.
  • Subdomains of the survey, which included communication, social, and repetitive behaviors were evaluated to see if there were differences within the various genetic conditions. This review found that there were relative strengths for certain genetic communities, such as 1q21 duplication carriers and communication, 16p11.2 deletion carriers and social domains, and HNRNPH2-related syndrome carriers and repetitive behaviors. There were also relative challenges for certain communities, such as communication for people with STXBP1-related syndrome, social behaviors for people with SCN2A-related syndrome, and repetitive behaviors for people with ASXL3-related syndrome and 15q11.2 deletion carriers.
  • The researchers noted that in general, the variability of the SCQ subdomain scores were greater within the results of people with a particular genetic condition, as compared with across genetic conditions. This suggests that a rare neurodevelopmental genetic variant on its own cannot predict if someone is going to have autism, and other genetic or environmental factors likely play a role.
  • This work was supported in part by a SFARI grant. Show Less
EBioMedicine 112, 105521 (2025)
Ali et al.
Full Article

15q11.2 deletion
16p11.2 deletion
16p11.2 duplication
1q21.1 deletion
1q21.1 duplication
ADNP
ASXL3
CTNNB1
DYRK1A
GRIN2B
HIVEP2
HNRNPH2
MED13L
PACS1
PPP2R5D
SCN2A
SETBP1
SLC6A1
STXBP1
SYNGAP1
2025